6-24480067-T-C

Variant names:

• chr6-24480067-T-C
• rs6911965
• NM_001503.4:c.154-108A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001503.4(GPLD1):​c.154-108A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 701,976 control chromosomes in the GnomAD database, including 8,361 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2653 hom., cov: 32)
  • Exomes 𝑓: 0.14 (5708 hom.)
• Consequence: GPLD1 NM_001503.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.91

Genes affected

GPLD1 (HGNC:4459): (glycosylphosphatidylinositol specific phospholipase D1) Many proteins are tethered to the extracellular face of eukaryotic plasma membranes by a glycosylphosphatidylinositol (GPI) anchor. The GPI-anchor is a glycolipid found on many blood cells. The protein encoded by this gene is a GPI degrading enzyme. Glycosylphosphatidylinositol specific phospholipase D1 hydrolyzes the inositol phosphate linkage in proteins anchored by phosphatidylinositol glycans, thereby releasing the attached protein from the plasma membrane. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPLD1	NM_001503.4	c.154-108A>G		intron_variant	Intron 2 of 24	ENST00000230036.2	NP_001494.2
GPLD1	XM_017010753.3	c.184-108A>G		intron_variant	Intron 3 of 25		XP_016866242.1
GPLD1	XM_047418658.1	c.184-108A>G		intron_variant	Intron 3 of 17		XP_047274614.1
GPLD1	XR_007059240.1	n.461-108A>G		intron_variant	Intron 3 of 26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPLD1	ENST00000230036.2	c.154-108A>G		intron_variant	Intron 2 of 24	1	NM_001503.4	ENSP00000230036.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25904 AN: 151758 Hom.: 2647 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.197

GnomAD4 exome AF: 0.136 AC: 74794 AN: 550100 Hom.: 5708 AF XY: 0.137 AC XY: 40610 AN XY: 295864

Gnomad4 AFR exome AF: 0.295

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.0835

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.193

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.151

GnomAD4 genome AF: 0.171 AC: 25935 AN: 151876 Hom.: 2653 Cov.: 32 AF XY: 0.174 AC XY: 12899 AN XY: 74232

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.195

Alfa AF: 0.124 Hom.: 2559

Bravo AF: 0.174

Asia WGS AF: 0.159 AC: 553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0060
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6911965; hg19: chr6-24480295;